A Functional Link between Housekeeping Selenoproteins and Phase II Enzymes

Authors

Aniruddha Sengupta, Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, CCR, NCI, NIH, Bethesda, MD
Bradley A. Carlson, Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, CCR, NCI, NIH, Bethesda, MDFollow
James A. Weaver, Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, CCR, NCI, NIH, Bethesda, MD
Sergey V. Novoselov, University of Nebraska-LincolnFollow
Dmitri E. Fomenko, University of Nebraska-LincolnFollow
Vadim N. Gladyshev, University of Nebraska-LincolnFollow
Dolph Hatfield, Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, CCR, NCI, NIH, Bethesda, MDFollow

Date of this Version

2008

Comments

Published in Biochem. J. (2008) 413, 151–161. (Printed in Great Britain) doi:10.1042/BJ20080277. Copyright © The Authors Journal compilation © 2008 Biochemical Society. Used by permission.

Abstract

Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes.